Arthropod repellent comprising extracts and/or parts of the plant vitex agnus-castus

ABSTRACT

The present invention includes portions or extracts of any kind, which can be obtained from the plant  Vitex agnus - castus  (monk pepper) and can be used as repellent against bothersome, lymph-and/or blood-sucking, skin penetrating, respectively food, storage materials—or plant—damaging arthropods (mites, ticks, insects). Thus, this repellent protects the health of humans, pet animals and livestock, plants and stored materials.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention includes portions or extracts of any kind, whichcan be obtained from the plant Vitex agnus-castus (monk pepper) and canbe used as repellent against bothersome, lymph- and/or blood-sucking,skin penetrating, respectively food-, storage materials—orplant—damaging arthropods (mites, ticks, insects). Thus, this repellentprotects the health of humans, pet animals and livestock, plants andstored materials.

2. State of the Art

A large diversity of arthropods attack the skin of humans and animals inorder to suck blood or lymph or lick body fluids or to dwell into theskin in order to feed upon tissues. Such nuisant arthropods are mites(e.g. biting and scabies mites), ticks (e.g. members of the generaIxodes, Rhipicephalus and argasids), mosquitoes (e.g. genera Anopheles,Culex, Aedes, Culiseta), simullids, gnats or ceratopogonids, flies (e.g.genera Lucilia, Sarcophaga, Musca, Stomoxys, Phlebotomus, Glossina),tabanids, fleas (e.g. cat fleas, jigger fleas), bugs, lice (e.g. head,body, crab). The members of the different groups of pests often occur inlarge numbers in nature and some enter buildings inhabited by humans andanimals. They molest their host by flight attacks (e.g. mosquitoes inhumans, flies in horses, simullids in cattle) and many are able totransmit a broad diversity of disease agents. Arthropod-borne diseasescan led to severe illness and death of humans (e.g. malaria, yellowfever, sleeping sickness, Chagas disease) and animals (e.g. borreliosis,babesiosis, theileriosis). Impact by arthropods and diseases theytransmit can also cause high economic losses (M. Rommel et al. 2000,Veterinärmedizinische Parasitologie, Parey, Berlin; H. Mehlhorn (ed.)2001, Encyclopedic references of parasitology. Vol. 1 and 2, Springer,New York, Heidelberg; J. M. Lachapelle, D. Tennstedt, L. Marot, 1997,Atlas of environmental dermatology, ULC Press, Louvain, Brussels),

Therefore, the search for compounds with a long-lasting, highlyeffective and safe protective activity is as old as human culture (H.Schlicher 1984, Aetherische Öle: Wirkungen und Nebenwirkungen, Dt.Apothekerzeltschrift 124: 1433-1442). Compounds protecting against theattacks of ectoparasitic arthropods are called repellents (O. Hansen andM. Londershausen 2001: ectoparasiticides. In: H.

Mehlhorn (ed.) 2001: Encyclopedic references of parasitology, Springer,Heidelberg, New York). In traditional medicine of many peoples all overthe world extracts of plants were used as repellents against attackingarthropods. Especially essential oils from peppermint, geranium,lavender, citronella, thyme, lemongrass, cedar, and extracts ofpennyroyal, eucalyptus and catnip have repellent properties (D. R.Barnard 1999. Repellency of essential oils to mosquitoes—diptera,Culicidae. J. Med. Entomol 36: 625-629; G. Nentwig 2003. Repellents,Parasitology Research 87: 214-216; H. Schlicher 1984, Aetherische Öle:Wirkungen und Nebenwirkungen. Dt. Apothekerzeltschrift 124: 1433-1442;A.Tawatsin et al. 2001. Repellency of volatile oils from plants againstmosquito vectors. J. Vector Ecol). For example patent DE 3901341A claimsa mixture of citronellol and eugenol as repellent against tissue mothsand cabinet beetles. However, to the prior art, plant derived productsdo not appear to repel insects as effective as chemicals like DEET. Themajority of products marketed by the industry to repel or killarthropods are based on chemically synthesized compounds (K. K. Buchel1970, Chemistry of plant protection against pesticides, In: R. Wegler,Chemle der Planzenschutz-und Schädlingsbekämpfungs-mittel, Vol. 1,Springer, Berlin, Heidelberg. New York). The most important syntheticrepellent is N,N-diethyl-m-toluamide (DEET), which is contained in manyproducts. Other registered repellents are dimethyl phthalate,2-ethyl-hexane-1,3-dol, isopulegol, 1-piperidine carboxylic acid andhydroxy-ethyl-isobutyl-piperidine-carboxylate (M. S. Tradin 1998.Mosquitoes and mosquito repellents: a clinician's guide. Ann. lnt, Med.128: 931-940).

A severe disadvantage of all until now described repellant extracts fromplants is the fact that they are predominantly effective only againstselected groups of arthropods or a very limited spectrum of suchtargets. In addition, they have another important drawback: the durationof protection that they confer is rather short (American PharmaceuticalAssociation, Washington D.C., Handbook of nonprescription drugs, 10thed.). Furthermore, essential oils often smell disagreable and may berefuted by humans and animals. Some animals, notably cats, get sick uponcontact with certain essential oils (e.g. tea-tree and thymian oil) (D.Villar et al, 1994. Toxicity of Melaleuca oil and related essential oilsapplied on dogs and cats. Vet. Hum. Toxicol. 36: 139-142). These animalsare unable to metabolize such oils due to the lack of certain necessaryenzymes. Furthermore, essential oils have high potencies to provoke skinirritations and allergies, so that many humans cannot use them (A. Wolf1999, Essential oil poisoning. J. Toxicol. Clin. Toxicol, 37: 721-727;S. Baum 2002, Aromatheraple: Zwischen Esotherik und Arznelmittelrecht,Pharm. Ztg. 147: 1208-1212). Essential oils easily permeate into theskin and also can carry other ingredients with them causing adverseeffects (A. C. Williams, B. W. Barry 1992. Skin absorption enhancers,Crit. Rev. Ther. Drug Carrier Sys. 9: 17-24). DEET has the disadvantagesthat it has an unpleasant odor, attacks plastic materials, may harmhealth and, it has a low efficiency against ticks and mites (H. Quiu etal. 1998. Pharmacokinetics, formulation, and safety of insect repellentN,N-diethyl-3-methylbenzamide (DEET): a review, J. Am. Mosq. Contr.Assoc, 14: 12-27; P. J. Robbins, M. G. Cherniak 1986. Review ofbiodistribution and toxicology of the insect repellentN,N-dlethyl-3-m-tolulamide (DEET). J. Toxicol. Environ. Hlth. 18:503-525). The compound Bayrepelhydroxy-ethyl-isobutyl-piperldine-carboxylate has much better propertiesas DEET, however, its activity against ticks is poor and it protectsagainst them just for about two hours. Bayrepel clearly does not protectsecurely during typical several hours lasting outdoor activitiesespecially in regions where many Ehrlichia-, virus- or Borrelia-infectedIxodes ticks occur,

In addition, none of the known plant extracts, DEET, Bayrepel, dimethylphthalate and other synthetic repellents have a sufficient effectivityagainst flies which molest e.g. horses and humans enormously in ruralregions. Also, known compounds of prior art have only a very limitedactivity against skin-penetrating, lymph- or bloodsucking arthropods. Nocompound is available which protects at the same time for at least 6 to8 hours against the attacks of ticks, mites, mosquitoes, flies,tabanids, fleas, bugs and lice, smells well, does not harm the health ofhumans, dogs, cats, horses and other house animals and is based on abloproduct (A. Turberg, 2001. Ectoparasiticides and repellents. In: H.Mehlhorn (ed.) 2001. Encyclopedic references of parasitology, Vol. 1 and2, Springer, Heidelberg, New York;http//www.holzer.li/repellentien.htm). In spite that there are somecompounds or combinations of plant extracts which have a good activityon a limited range of insects, there is not yet available a product,which protects equally efficient against all attacks of ticks, mites andvarious insects. However, such a broad-spectrum of protection is neededfor usual outdoor activities, since the wanderer cannot foresee, whetherhe and his dog will be target either of flies, mosquitoes, fleas, ticks,mites, tabanids, gnats or all of them. Especially in the case of ticks,mites and flies there is no product on the market, that provides secureprotection against attacks.

JP-A-07-0170710 discloses a vermin repellent containing2-(2-formyl-3-methyl-cyclopent-2-enyl)acetaldehyde as an activecomponent. The compound can be produced by extracting the leaf of freshHAMAGO (Vltex rotundifolia), which is different from Vitex agnus-castus,collected in Tanegashima Island with chloroform, distilling out thesolvent, distilling the obtained concentrate under reduced pressure toobtain a volatile fraction and finally subjecting the fraction to silicagel thin-layer chromatography. The agent is told to be effective againstblood-sucking vermin such as Aedes, Culices, gnat and Stomoxyscalcitrans. No activity is however reported against for example ticks ormites, and its activity against these is in fact low or even not there.

Clearly there is a need for a repellent that is long-lasting effectiveagainst, in particular, ticks and insects, and that is save and pleasantto use. Thus, there is a strong need of a broad-spectrum repellentoffering at the same time a protection of humans and animals against theuntil now not limited attacks of ticks, mites and flies. The task of thepresent invention is the presentation of a long-lasting (i.e. 8 hours)broad-spectrum-repellent—being active as well against ticks and mites asagainst an extremely wide range insects. This problem is solved by thepresent invention as defined in the claims and the followingdescription.

SUMMARY OF THE INVENTION

Surprisingly it was found that the plant Vitex agnus-castus, includingextracts, parts and other active components thereof, offer along-lasting protection as well against ticks and mites as against alarge variety of insects. This is not the case when using the knownnatural products or synthesized compounds. A further advantage of thepresent invention is that extracts of Vitex agnus-castus do not containnoxious constituents, which might harm the health of humans or animals.Vitex agnus-castus is a well known in phytomedicine for other types oforal treatments of patients. It is used to treat female hormonaldisorders, e.g. premenstrual syndrome, menopausal symptoms, acne, or topromote milk flow (D. Brown 1994, Herbal Research review: Vitexagnus-castus Clinical Monograph. Quarterly Review of Natural Medicine; DJ. Schellenberg 2001; Treatment for the premenstrual syndrome withagnus-castus fruit-extract: prospective, randomized, placebo controlledstudy. BMJ 322: 134-137). The constituents of Vitex agnus-castus—sinceapplied as herbal medicine since ancient times—had been thoroughlytested on found to be safe regarding side effects (J. Schellenberg 2001,see above; W. Hager 1990, Hager's Handbook of the Pharmaceutical Praxis,5th ed.). Skin irritation and allergies, which may be provoked byapplication of several other repellents, that contain essential oils,are unknown to develop upon long-lasting use of Vitex agnus-castus. Incontrast to other repellents the extracts of Vitex agnus-castus do notsmell strong. Therefore, it is easy to produce convenient repellents fordaily use offering a high satisfaction to of the user. Extracts of Vitexagnus-castus can be used without any side effects on the health ofhumans and animals offering a broad spectrum protection againstmolesting arthropods (e.g. flies) or vectors of agents of diseases (e.g.borreliosis, ehrlichlosis via ticks, malaria, dengue, yellow fever, Westnile fever via mosquitoes). This protection can be provided to both,humans and animals.

Moreover, extracts of Vites agnus-castus are not detrimental to plantsor natural storage materials. Hence, extracts of Vitex agnus-castus canbe safely applied to protect such materials against pest organisms.

It is also an advantage that the plant Vitex agnus-castus is found inthe wild throughout large regions at the Mediterranean Sea and in manyregions of West Asia. The plant is also grown on commercial plantationsin many subtropical countries. Thus, the raw material of Vitexagnus-castus are easily available for commercial expoitation. Of notableimportance is the fact, that many consumers prefer nature-derivedproducts over of synthetical chemicals.

PRODUCTION OF REPELLENTS ACCORDING TO INVENTION

To produce the claimed repellents preferably semen and leafs are used,but also branches or roots may also be used. One easy possibility ofproduction starts with the mincing of the plant portions in a grinderand to extract the compounds by adding the plant powder watery ororganic solutions (e.g. ethanol or isopropanol) or via CO₂ or steamdistillation. In this respect it is for example referred to US2003/0054058 A1 included here by reference. Finally, the obtained plantextracts become mixed with different additives such as suitablecarriers, including water, alcohols such as ethanol, isopropanol orglycerol, polyethyleneglycol, and tensids, emulgators, perfumes,thickening agents, stabilisators, antioxidants, fixatives orpreservatives in order to obtain the final product. Favourableformulations of repellents from Vitex agnus-castus contain the oilyextract of the plant in an amount of 0.05-100% (volume/volume),preferably 0.5-33% (v/v) and most preferably percentages of 1-7% (v/v).

EXAMPLES

In order to demonstrate the unique capability of the inventive repellentthe following examples are provided.

Semen of Vitex agnus-castus were powdered, 15 g of this powder weresoaked in 75 ml acetonitrile and incubated overnight. The extract wasfiltrated through a paper filter and the solvent was completelyevaporized at room temperature. One ml of the oily extract wassolubilized with 4 ml of a solution consisting of 50% water, 20%genapol, 20% ethanol and 10% polyethyleneglycol 300. This repellentformulation was used for the following tests.

1. Tick Species (Ixodes Ricinus, Rhipicephalus sanguineus)

-   A. Balb/c mice (in a cage) were slightly covered (by spraying) with    the repellent. Beginning immediately after the spraying and then    after 1, 2, 3, 4, 5, 6, 7, 8 hours ticks were placed onto the hair    of the mice. It was seen that these ticks immediately left the mice    and hided in a corner for more than 8 hours, while after 4 hours 8    of 10 ticks on untreated mice were firmly attached to the skin,-   B. The same experiment was done with two cats and two dogs with the    same results. In all cases the ticks fled from the treated animals.    2. Flies (Sarcophaga carnaria, Grey Flesh Fly)

Hands covered with latex gloves were sprayed with the repellent or not(control). Then the hands were put into a cage with 500 adult flies for3 minutes. The number of approaches, the touch downs and the time ofsitting was noted. It turned out that during the first 3 hours manyflies approached, but did not sit down. During the next 5 hours only 4-7specimens out of 30 approaching ones touched the skin, but left itwithin 1-2 seconds. In the case of untreated control hands the fliesapproached from the very beginning and sat there for often more than10-15 seconds,

3. Stable Flies (Stomoxys calcitrans)

An uncovered hand was sprayed with the repellent. Then it was introducedinto a cage containing 50 hungry flies at intervals of 30 minutes. Thesecond hand of the same person remained untreated and was used ascontrol. The approaches within 5 minutes were counted. It was noted thatthe stable flies did not approach to the treated hand for 4 hours andthat later (until 7 hours) only a quarter or even only a tenth of theflies approached, while in the case of the control hand biting occurredimmediately after introducing the hand into the cage.

4. Cat Flea (Ctenocephalides fells)

Balb/c mice in a cage were sprayed with the repellent or not (controls)and put into cages with 50 hungry fleas. At intervals of 30 minutes itwas controlled whether the fleas infested on the skin of the treatedmice. While in the case of the untreated controls the fleas attachedimmediately to the mice, fleas left for 6 hours urgently the hair oftreated mice in case they came into contact with these hair. For exampleafter 6 hours of exposition 4 out of 50 fleas were found on the groundof the cage while one was free inside the hair and only one startedsucking.

5. Mosquitoes (A. maculipennis, A. aegyptiand C. pipiens)

One the hand of a volunteer was sprayed with the repellent, the otherhand not (control). The hand were introduced for 3 minutes at intervalsof 1 hour into a cage containing about 500 hungry females. Within 8hours no mosquito was seen to touch down on a treated region, while atthe untreated hand blood sucking started immediately.

6. Lice (Adults and Nymphs of Pediculus humanus corporis)

On a piece of white tissue a circle was drawn with the repellent. Then50 lice were placed into the center of this circle. Lice approaching theborder of the circle stopped and moved immediately backwards. In casethey were placed onto the sprayed place the left it immediately.

7. Moths (of Cloths)

When moths were placed onto tissue treated with the repellent they leftit immediately within the 6 hours of observation, while they stayed onuntreated tissues for long.

In addition, numerous other tests were conducted with varyingcompostions and test animals, with the examples provided belingrepresentative samples of the testing program which was conducted.

EXAMPLES OF FORMULATION

Since a repellent—besides its claimed repellent activity—should haveskin—caring—properties and propagation of well smelling odour, which aredepending on personal preferences, there exist many possibilities offormulations. Thus the following examples are only few of the possiblecombinations:

1. Repellent as Spray: Odour Nature, i.e. Cool and Smelling like Meadowand Forest

-   10 g powdered semen of Vitex agnus-castus are mixed with 100 ml of    70% ethanol for 24 hours. Then the extract is filtered and is mixed    without previous vaporization with the following ingredients:-   33 ml ethanolic extract of Vitex agnus-castus,-   20 ml glycerol, perfumes, citric acid,-   water ad 100 ml    2. Repellent as Spray with a Note of Refreshing Citrus:-   33 ml ethanolc extract of Vitex agnus-castus,-   4 ml genapol®X-080 (Hoechst AG),-   0.3 ml lemongrass oil,-   water ad 100 ml    3. Repellent as Lotion

In order to obtain the repellent by steam distillation 100 g of mincedleafs of Vitex agnus-castus were mixed with 300 ml water in a distillerybottle, which is heated up (in a paraffin bath) to 120° C. until thewater is evaporized. The steam is collected and cooled down. The oilyphase of the distilled product is separated from the aqueous layer. Thefollowing compounds were added one after the other and heated to 70° C.:

-   2 ml oily extract of Vitex agnus-castus,-   7 ml petrolatum,-   5 ml glycerol,-   5 ml isopropylpalmitate,-   3 ml cetylalcohol,-   1 ml di-stearyl dimethyl ammonium chloride,-   1 ml dimethicone,-   0.6 ml phenoxyethanol,-   water ad 100 ml    4. Repellent against Moths of Clothes

10 g semen of Vitex agnus-castus were included into a closed papersacklet. This sacklet is enveloped in an aluminium foil in order toavoid loss of odour when being stored prior to use.

The given examples are intended as representative formulations ofcompostions of this invention and are not intended to limit, in anymanner, the breadth or scope of the present invention.

1. A repellent against infestation of arthropods comprising extracts,and/or parts of the plant Vitex agnus-castus.
 2. The repellent of claim1 against infestation of arthropods in humans and pet or food animals orformulated for protection of plants or stored materials comprisingextracts or parts of the plant Vitex agnus-castus.
 3. The repellent ofclaim 1, wherein portions of the plant or extracts of the semen, fruits,leafs, stalks or roots of Vitex agnus-castus are used.
 4. The repellentof claim 1, which is used against ticks or mites.
 5. The repellent ofclaim 1, which is used against files or tabanlds.
 6. The repellent ofclaim 1, which is used against simullids, ceratopogonids, gnats or sandflies.
 7. The repellent of claim 1, which is used against mosquitoes. 8.The repellent of claim 1, which is used against fleas.
 9. The repellentof claim 1, which is used against lice (including head lice, body lice,crab lice).
 10. The repellent of claim 1, which is used against bugs(including bed bugs, predatory bugs).
 11. The repellent of claim 1,which is employed to protect against the bites of lymph—or blood suckinginsects and other arthropods.
 12. The repellent of claim 1, which isused to protect against skin-penetrating arthropods.
 13. The repellentof claim 1, which is characterized by the fact that it protects againsttransmission of agents of diseases.
 14. The repellent of claim 1, whichis employed to protect plants or stored materials, including textiles,furs, food and other agricultural products.
 15. The repellent of claim1, comprising at least one dermatologically acceptable carrier.
 16. Therepellent of claim 1, comprising at least one ingredient used for skincare of humans or animals.
 17. The repellent of claim 1, comprising atleast one perfume.
 18. The repellent of claim 1, comprising at least oneadditive which increase the stability of the product, includingantioxidants such as 6-O-palmitoyl-L-ascorblc acid or2,6-Di-tert.-butyl-4-methylphenol.
 19. The repellent of claim 1,comprising at least one UV absorber, including titaniumoxid oroctylmethoxycinnamate.
 20. The repellent of claim 1, comprising at leastone further repellent compound, including essential oils of otherplants, N,N-diethyl-m-toluamide (DEET), dimethyl phthalate,N,N-dlethylbenzamide, 2-ethyl-hexane-1,3-diol, p-methane-3,8-diol,isopulegol, 1-piperidine carboxylic acid,hydroxy-ethyl-isobutylpiperidine-carboxylate, derivatives and mixturesthereof.
 21. Use of extracts, parts, and/or other active components ofVitex agnus-castus against infestation of arthropods.
 22. Use of claim21 against infestation of arthropods in humans, pet or food animals,plants or stored materials including textiles, furs, food andagricultural products.
 23. Use of claim 21 for external application. 24.Use of claim 21 in the form of repellent which is in the form of asolution, spray, aerosol, lotion, gel, creme, powder, perfume, sunfilter or deodorant.
 25. Use of claim 21 for application on skin, hair,clothes.
 26. Use of a plant of the genus vitex for the preparation of arepellent against ticks and/or mites.
 27. Use of claim 26 against ticks.